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Biomedical subjects

H Kakinuma

Publications and source records attributed to H Kakinuma.

At least 37 records · Page 2Linked to original sources
PubMed1998

Mouse forkhead (winged helix) gene LUN encodes a transactivator that acts in the lung.

Many transcription factors involved in the determination and maintenance of cell fates share DNA-binding motifs to form gene families. The most recently discovered evolutionarily conserved DNA-binding domain of 100 amino acids, termed the forkhead domain, emerged from a sequence comparison of the rat transcription factor HNF-3 alpha and the homeotic gene fork head of Drosophila. Here we describe the isolation of a new mouse forkhead gene named LUN. Of a total of five forkhead genes in the lung, the LUN gene was uniquely expressed in the bronchiolar epithelium and in type II pneumocytes. We found that the LUN protein has forkhead domain that is identical to the HFH8 gene and a C-terminal region that is very similar to the HFH8 gene. Based on the structural similarity of the two proteins, we investigated the structure-function relationship of the LUN protein in two kinds of promoters and found that regions C and D work differently as activation domains, namely that region C acts autonomously but region D cannot work without region C. These results suggest that the LUN gene may play an important role as a transactivator in the determination and maintenance of some types of cells in the lung.

Animals↗
PubMed1998

Characterization of Clostridium botulinum type B neurotoxin associated with infant botulism in japan.

The neurotoxin of strain 111 (111/NT) associated with type B infant botulism showed antigenic and biological properties different from that (Okra/NT) produced by a food-borne botulism-related strain, Okra. The specific toxicity of 111/NT was found to be about 10 times lower than that of Okra/NT. The monoclonal antibodies recognizing the light chain cross-reacted with both neurotoxins, whereas most of the antibodies recognizing the carboxyl-terminal half of the heavy chain of Okra/NT did not react to 111/NT. Binding experiments with rat brain synaptosomes revealed that 125I-labeled 111/NT bound to a single binding site with a dissociation constant (Kd) of 2.5 nM; the value was rather lower than that (0.42 nM) of 125I-Okra/NT for the high-affinity binding site. In the lipid vesicles reconstituted with ganglioside GT1b, 125I-Okra/NT interacted with the amino-terminal domain of synaptotagmin 1 (Stg1N) or synaptotagmin 2 (Stg2N), fused with the maltose-binding protein, in the same manner as the respective full-length synaptotagmins, and the Kd values accorded with those of the low- and high-affinity binding sites in synaptosomes. However, 125I-111/NT only exhibited a low capacity for binding to the lipid vesicles containing Stg2N, but not Stg1N, in the presence of ganglioside GT1b. Moreover, synaptobrevin-2, an intracellular target protein, was digested to the same extent by the light chains of both neurotoxins in a concentration-dependent manner. These findings indicate that the 111/NT molecule possesses the receptor-recognition site structurally different from Okra/NT, probably causing a decreased specific toxicity.

Animals↗
PubMed1998

Synthesis and antifungal activity of novel thiazole-containing triazole antifungals. II. Optically active ER-30346 and its derivatives.

A series of novel thiazole-containing triazole antifungals was synthesized and evaluated for antifungal activity against a variety of clinically isolated pathogenic fungi in vitro and against systemic candidosis in vivo. These compounds showed potent antifungal activities in vitro and in vivo. In particular, (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4- difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (12g; ER-30346) showed potent and well-balanced in vitro activities and potent in vivo efficacy, and had a good safety profile.

Animals↗
PubMed1998

Mitochondrial DNA point mutation at nucleotide pair 3316 in a Japanese family with heterogeneous phenotypes of diabetes.

A mitochondrial DNA (mtDNA) point mutation at nucleotide pair (np) 3316 has been reported in relation to diabetes. We recently encountered a non-obese family with this type of mutation. The proband in the affected family, a 49-year-old woman who had been previously diagnosed as having an insulin-requiring non-insulin-dependent diabetes mellitus (NIDDM), was referred to our hospital for treatment of diabetic gangrene in her left foot. Her insulin secretory capacity was markedly reduced, but the insulin sensitivity evaluated by the euglycemic hyperinsulinemic clamp technique was normal. In addition, her serum lactate level was markedly increased after a 5 min ambulation, although her serum pyruvate and ketones remained within the normal range. Twenty-year-old twin sons had been treated with insulin since the age of 7, when both were diagnosed with insulin-dependent diabetes mellitus (IDDM). The proband's mother, a 68-year-old, was nondiabetic at this time. MtDNA analysis revealed a point mutation at np 3316 in all family members, which was homoplasmic for the mutation on a photograph of agarose gel electrophoresis containing ethidium bromide under ultraviolet light. This mutation seemed to be maternally transmitted in the family, and the onset of diabetes was occurring earlier and the insulin secretory capacity was declining from generation to generation, so that these findings suggest that the point mutation at np 3316 is associated with various phenotypes of diabetes.

DNA, Mitochondrial↗
PubMed1998

Expression of vascular endothelial growth factor gene and its receptor (flt-1) gene in urinary bladder cancer.

We investigated expression of the vascular endothelial growth factor (VEGF) gene and its receptor gene (flt-1) in 30 patients with transitional cell carcinoma (TCC) of the urinary bladder by Northern blot hybridization analysis. The VEGF transcript was observed in all of the tumors and the normal mucosae. Of the 20 tumors in which a comparative study was done, eight (40.0%) overexpressed the gene with a tumor versus normal ratio of equal to and greater than 3.0. Invasive TCCs expressed significantly more VEGF gene than superficial TCCs. Cytoplasm of tumor cells was positively stained by immunohistochemistry with an anti-VEGF monoclonal antibody, while the intratumoral endothelial cells and the vascular smooth muscle cells were weakly positive for the staining. TCCs, normal mucosae and human umbilical endothelial cells expressed flt-1 gene, while leucocytes from peripheral blood did not. The expression level of flt-1 gene significantly correlated with that of the VEGF gene in the tumor. These results indicate that the VEGF gene is frequently overexpressed in TCC of the urinary bladder, especially in muscle invasive tumors, and that a paracrine system including VEGF and flt-1 exists between the TCC cells and the adjacent endothelial cells so as to regulate the angiogenesis in this tumor.

Adult↗
PubMed1997

Isolation of the mouse (MFH-1) and human (FKHL 14) mesenchyme fork head-1 genes reveals conservation of their gene and protein structures.

The very recently found evolutionarily conserved DNA-binding domain of 100 amino acids, termed the fork head domain, emerged from a sequence comparison of the rat hepatocyte transcription factor HNF-3 alpha and the homeotic gene fork head of Drosophila. We previously isolated a new member of this family, the mesenchyme fork head-1 (MFH-1) gene, which is expressed in developing mesenchyme. Here we describe the isolation of the mouse (MFH-1) and human (FKHL14) chromosomal MFH-1 genes and the determination of the gene and protein structures of MFH-1. We found that the MFH-1 gene has no introns and that the identity of the amino acid sequences of mouse and human MFH-1 proteins is 94%. We also investigated the transcriptional activity of the mouse and human MFH-1 proteins and found that both proteins act as positive transactivators.

Amino Acid Sequence↗
PubMed1997

Application of nested polymerase chain reaction for the rapid diagnosis of infant botulism type B.

A nested polymerase chain reaction was utilized to successfully detect the type B botulinum neurotoxin gene of Clostridium botulinum in feces from a 6-month-old patient, who had already been diagnosed with type B infant botulism by mouse bio-assay. This method of rapid diagnosis without enrichment culture of feces can be applied to other types of toxins in the use of the type-specific primers. Further investigations, however, are required to define the sensitivity and specificity of the method.

Biological Assay↗
PubMed1997

Essential roles of the winged helix transcription factor MFH-1 in aortic arch patterning and skeletogenesis.

Mesenchyme Fork Head-1 (MFH-1) is a forkhead (also called winged helix) transcription factor defined by a common 100-amino acid DNA-binding domain. MFH-1 is expressed in non-notochordal mesoderm in the prospective trunk region and in cephalic neural-crest and cephalic mesoderm-derived mesenchymal cells in the prechordal region of early embryos. Subsequently, strong expression is localized in developing cartilaginous tissues, kidney and dorsal aortas. To investigate the developmental roles of MFH-1 during embryogenesis, mice lacking the MFH-1 locus were generated by targeted mutagenesis. MFH-1-deficient mice died embryonically and perinatally, and exhibited interrupted aortic arch and skeletal defects in the neurocranium and the vertebral column. Interruption of the aortic arch seen in the mutant mice was the same as in human congenital anomalies. These results suggest that MFH-1 has indispensable roles during the extensive remodeling of the aortic arch in neural-crest-derived cells and in skeletogenesis in cells derived from the neural crest and the mesoderm.

Animals↗
PubMed1997

Synthesis and antifungal activity of novel thiazole-containing triazole antifungals.

A new series of thiazole-containing triazole antifungals was synthesized and evaluated for antifungal activity against a variety of clinically isolated pathogenic fungi in vitro and against systemic candidosis in vivo. Among these compounds, (+/-)-1-(2,4-difluorophenyl)-1-[4-(2,4-difluorophenyl) thiazol-2-yl]-2-(1H-1,2,4-triazol-1-yl)ethanol (ER24161) showed the most potent and well-balanced in vitro activities and excellent in vivo efficacy. We also achieved an enantioselective synthesis of the more potent enantiomer of ER-24161.

Animals↗
PubMed1996

Synthesis of 1',6'-disubstituted sucroses and their behavior as glucosyl donors for a microbial alpha-glucosyltransferase.

Versatile 6'-chloro-6'-deoxy-1'-substituted sucrose derivatives were synthesized in search of an optimum donor substrate for the intermolecular transglucosylation with the alpha-glucosyltransferase from Protaminobacter rubrum. Two substituents at the C-1' and C-6' positions of sucrose were introduced utilizing the distinct reactivity of the corresponding sulfonates. Methyl beta-D-arabinofuranoside was most efficiently glucosylated with the 1'-deoxy derivative 5. Hydroxyl and fluoro groups at C-1' show a tendency to enhance the intramolecular transglucosylations, giving 3-O-(alpha-D-glucopyranosyl)-D-fructose derivatives.

Bacteria↗
PubMed1996

Targeted cancer chemotherapy with arterial microcapsule chemoembolization: review of 1013 patients.

To evaluate the feasibility of intraarterial infusion of microencapsulated anticancer drugs (chemoembolization), collective data on 1013 cancer patients were reviewed. Ethylcellulose microcapsules containing mitomycin C (median total dose 20 mg), cisplatin (60 mg) or peplomycin (40 mg) were given to tumor-feeding arteries by bolus infusion in 79% of the patients and by fractionated infusion in the others, as a palliative (71%) or preoperative measure (29%). The target sites were the liver (42%), kidney (24%), intrapelvic organs (18%), lung (4%), head and neck (3%), bone (1%) and others (9%), excluding the central nervous system and gastrointestinal tract. The incidence of overall adverse effects ranged from 0.2 to 54.9%, but grade 2-3 hematological, renal and hepatic toxicities, local pain, abdominal discomfort, cutaneous reaction, remote embolization and infection were < 10%. Nine patients (0.9%) in the early stages of trials suffered serious complications including treatment-related death in two with critical underlying diseases of the target organs. The remaining patients recovered from the adverse effects, except for grade 2 cutaneous reactions, within 2 months by routine palliative measures. A > or = 50% tumor reduction was seen in 28% of 427 evaluable tumors (42% for < 25-cm2 tumors and 20% for > or = 25-cm2 tumors) with a median treatment number of one. The response rate depended on both the tumor size and the treatment number (P < 0.05), but it was not affected by prior therapies. Mitomycin C microcapsules produced a higher response rate. Complete or partial remission of intractable pain and genitourinary gross hemorrhage was found in two-thirds of eligible patients. The results indicate that this treatment modality, though restricted by catheter technique, can be applied to various tumor lesions with an acceptable morbidity and prospective trials are justified to evaluate the potential role of such a targeted chemotherapy.

Adolescent↗
PubMed1996

Pruritic papular eruptions and candidiasis due to HIV infection.

We present two patients with refractory papular eruptions and severe candidiasis. Both of them are positive for treponema pallidum and have suffered from pruritic papular eruptions (PPE) that had resisted therapy for years. Also, candidiasis appeared in the mouth, at intertriginous sites, and on the feet. The clinical features suggested immunodeficiency, and HIV tests were positive. Histologically, the specimen from the PPE lesion showed perivascular and perifollicular mixed cell infiltration. The fungus was identified by both Parker-KOH-mount examination and mycologic culture as Candida albicans. The pruritic papules were healed almost completely with oral antihistamine and topical corticosteroid treatment, and the candidiasis mostly disappeared after treatment with topical antifungal agents alone. We learned from these two cases that refractory PPE and severe candidiasis indicate a need for HIV testing.

AIDS-Related Opportunistic Infections↗
PubMed1996

The first case of type B infant botulism in Japan.

A six-month-old girl with a 5 consecutive day history of constipation and poor feeding developed generalized weakness, poor head control, difficulties in sucking and swallowing, and cranial nerve dysfunction within a few days. These characteristic manifestations and clinical course prompted examination of the possibility of infant botulism, although no history of eating honey was obtained. Mouse bioassay performed with enema effluent demonstrated type B botulinum toxin. Culture of the effluent was positive for Clostridium botulinum type B. This is the first case of type B infant botulism in Japan.

Animals↗
PubMed1996

[Prognostic importance of prostate specific antigen in patients with hormonally treated stage D2 prostate carcinoma].

BACKGROUND: The objective of this study is to evaluate the relationship between PSA value and prognosis of the patients with stage D2 prostate carcinoma. METHODS: Serum prostate specific antigen was analyzed in 61 patients with stage D2 prostate carcinoma submitted to hormone therapy. RESULTS: The median values of PSA parameters were 77.6 ng/ml for the initial PSA, 91.8% for the maximal decrease, 2.7 ng/ml for the nadir, 1.1 months for the half-time time, 3.0 months for the time to nadir, 3.2 months for the doubling time after progression and 0.39 for the ratio of antemortem versus initial PSA. The median biochemical progression-free time was 15.0 months and the median actuarial survival after progression was 24.9 months. The progression-free time was significantly correlated with the normalization of PSA (p < 0.001) and the initial PSA of less than 100 ng/ml (p < 0.05), and the survival time after progression was significantly correlated with the doubling time (p < 0.05). The normalization of PSA was affected by initial value, maximal decrease rate and half-life time of PSA respectively, but not by the histological grade of the primary tumors. The doubling time was not correlated with these factors nor with the progression-free time. CONCLUSION: The results show that the initial value, nadir level and doubling time of PSA can be used as prognostic parameters for prostatic carcinoma. Both the low ratio of premortem versus initial PSA, which may reflect an increase of stem cell fraction, and the PSA doubling time after relapse, which seems similar to or shorter than that of untreated cases, will indicate an aggressive potential of hormone-refractory tumors.

Aged↗